Healthy newborn infants do not bleed despite low levels of blood coagulation factor activities. Hemorrhage or thrombosis is, however, found in 40% of neonatal deaths and is often associated with hypoxemia, acidosis, hypercarbia, and hemorrhage with hypotension. The chronically catheterized fetal lamb model allows for study of normal blood coagulation throughout gestation and for studies of the effects of individual stresses and hormones on this developing system. Low levels of protein C and/or differences between adult and fetal vascular endothelium, with respect to release of hemostatically important mediators, (prostacyclin, plasminogen activator, angiotensin convering enzyme) may explain the lack of bleeding in the healthy newborn. Measurements of plasma protein C and the release of hemostatic mediators by vascular endothelium from fetal lambs at different gestational ages, are proposed. Certain hormones (cortisol, thyroxin, insulin) may also influence blood coagulation in the fetus and newborn. Controlled studies of the effects of these hormones on blood coagulation in the fetus, and the potential for initiating the effects by treating the mother, are to be carried out. The ability of the normal newborn lamb to increase the synthesis of fibrinogen, in response to inflammation and fibrinogen degradation products, is to be measured using radioisotope incorporation. Changes in synthesis are to be correlated with changes in hepatocyte fibrinogen antigen. Fibrinogen antigen will be measured in isolated hepatocytes using fluorescently labelled antifibrinogen antibody and the Fluorescence Activated Cell Sorter. Studies of the effects of acidemia, hypercarbia and blood loss with hypotension on blood coagulation and organ blood flow in the chronically catheterized fetal lamb will be carried out. Knowledge of the normal development of blood coagulation and vascular endothelium and the effects of the stresses and hormonal changes on this developing system will provide the information necessary for interpreting changes in coagulation following premature delivery. The studies will provide information that should lead to improved measures for the diagnosis, treatment and prevention of hemorrhage and thrombosis in the newborn.